Biotherapeutic Agents and Disease in Infants

  • Larry K. Pickering
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 501)


Human milk contains many factors that act synergistically or with redundancy in protecting suckling infants from infectious diseases. The rigorous application of the scientific method has shown significant beneficial effects of these specific factors. The beneficial effects of biotherapeutic agents, including prebiotics and probiotics, on the alteration of intestinal microflora and modulation of the local and systemic immune response of infants have been shown. The beneficial effects of these compounds on preventing diarrhea and possibly other infectious diseases in infants serves as a model for the development and use of biotherapeutic agents to treat and prevent infectious diseases in persons of all ages.


Human Milk Intestinal Microflora Lactobacillus Acidophilus Lactobacillus Species Acute Diarrhea 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alak JIB, Wolf BW, Mdurvwa EG, Pimentel-Smith GE, Adeyemo O. Effect of Lactobacillus reuteri on intestinal resistance to Cryptosporidium parvum infection in a murine model of acquired immunodeficiency syndrome. J Infect Dis 1997;175:218–221.PubMedCrossRefGoogle Scholar
  2. Alm L. The effect of Lactobacillus acidophilus administration upon the survival of Salmonella in randomly selected human carriers. Prog Food Nutr Sci 1983;7:13–17.PubMedGoogle Scholar
  3. Antony SJ, Stratton CW, Dummer JS. Lactobacillus bacteremia: description of the clinical course in adult patients without endocarditis. Clin Infect Dis 1996;23:773–778.PubMedCrossRefGoogle Scholar
  4. Axelsson L, Chung T, Dobroqosz W, Lingren S. Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microbiol Ecol Health Dis 1998;2:131–136.CrossRefGoogle Scholar
  5. Balmer SE, Wharton BA. Diet and faecal flora in the newborn: breast milk and infant formula. Arch Dis Child 1989;64:1672–1677.PubMedCrossRefGoogle Scholar
  6. Beaudry M, Dufour R, Marcoux S. Relations between infant feeding and infections during the first six months of life. J Pediatr 1995;126:191–197.PubMedCrossRefGoogle Scholar
  7. Beerens H, Romond C, Neut C. Influence of breast-feeding on the bifid flora of the newborn intestine. Am J Clin Nutr 1980;33:2434–2439.Google Scholar
  8. Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol 1984;28:975–986.PubMedGoogle Scholar
  9. Biller JA, Katz AJ, Flores AF, Buie TM, Gorbach SL. Treatment of recurrent Clostridium difficile colitis with Lactobacillus GG. J Pediatr Gastroenterol Nutr 1995;21:224–226.PubMedCrossRefGoogle Scholar
  10. Buddington R, Williams C, Chen S-C, Witherly S. Dietary supplement of neosugar alters the fecal flora and decreases activities of some reductive enzymes in human subjects. Am J Clin Nutr 1996; 63:709–716.PubMedGoogle Scholar
  11. Bullen CL, Tearle PV, Willis PT. Bifidobacteria in the intestinal tract of infants: an in vivo study. J Med Microbiol 1976;9:325–333.PubMedCrossRefGoogle Scholar
  12. Campbell J, Bauer L, Fahey G, Hogarth A, Wolf B, Hunter D. Selected fructooligosaccharide (1-Kestose, Nystose, and 1F43-Fructofuranosylnystose) composition of foods and feeds. J Agric Food Chem 1997;45:3076–3082.CrossRefGoogle Scholar
  13. Czeruka D, Rouk I, Rampal P. Saccharomyces boulardii inhibits secretagogue-mediated adenosine 3’,5’ cyclic monophosphate induction in intestinal cells. Gastronenterology 1994;106:65–72.Google Scholar
  14. Pozo-Olano J, Warram JH Jr, Gomez RG, Cavazos MG. Effect of a lactobacilli preparation of travelers’ diarrhea. A randomized, double blind clinical trial. Gastroenterology 1978;74:829–830.Google Scholar
  15. Duffy LC, Byers TE, Riepenhoff-Talty M, LaScolea LJ, Zielezny M, Ogra PL. The effects of infant feedingon rotavirus-induced gastroenteritis. A prospective study. Am J Public Health 1986a;76:259–263.CrossRefGoogle Scholar
  16. Duffy LC, Riepenhoff-Talty M, Byers TE, La Scolea LJ, Zielezny MA, Dryja DM, Ogra PL. Modulation of rotavirus enteritis during breast-feeding. Implications on alterations in the intestinal bacterial flora. Am J Dis Child 1986b;140:1164–1168.Google Scholar
  17. Duffy LC, Zielezny MA, Riepenhoff-Talty M et al. Effectiveness of Bifidobacterium bifidium in mediating the clinical course of murine rotavirus diarrhea. Pediatr Res 1993;33:983.Google Scholar
  18. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents: A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870–876.PubMedCrossRefGoogle Scholar
  19. Foster TL, Winans L, Carski TR. Evaluation of lactobacillus preparations of enterotoxigenic Escherichiacoli-induced rabbit ileal loop reactions. Am J Gastroenterol 1980;73:238–243.PubMedGoogle Scholar
  20. Fukushima Y, Kawata Y, Hara H, Terada A, Mitsuoka T. Effect of a probiotic formula on intestinal immunoglobulin A production in healthy children. Int J Food Microbiol 1998;42:39–44.PubMedCrossRefGoogle Scholar
  21. Fuller R. Probiotics in human medicine. Gut 1991;32:439–442.PubMedCrossRefGoogle Scholar
  22. Fuller R, Gibson G. Modification of the intestinal microflora using probiotics and prebiotics. Scand J Gastroenterol 1997;32:28–31.Google Scholar
  23. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125:1401–1412.PubMedGoogle Scholar
  24. Gorbach SL, Chang TW, Goldin B. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet 1987;2:15–19.Google Scholar
  25. Guarino A, Canani R, Spagnuolo M, Albano F, DiBenedetto L. Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr 1997;25:516–519.PubMedCrossRefGoogle Scholar
  26. Husni RN, Gordon SM, Washington JA, Longworth DL. Lactobacillus bacteremia and endocarditis: review of 45 cases. Clin Infect Dis 1997;25:1048–1055.PubMedCrossRefGoogle Scholar
  27. Isolauri E, Juntenen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacilluscasei sp. strain GG) promotes recovery from acute diarrhea in children. Pediatrics 1991;88:90–97.PubMedGoogle Scholar
  28. Isolauri E, Kaila M, Mykkanen H, Ling WH, Salminen S. Oral bacteriotherapy for viral gastroenteritis. Dig Dis Sci 1994;39:2595–2600.PubMedCrossRefGoogle Scholar
  29. Isolauri E, Joensuu J, Suomalainen H, Luomala M, Vesikari T. Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine 1995;13:310–312.PubMedCrossRefGoogle Scholar
  30. Kaila M, Isolauri E, Soppi E, Virtanen E, Laine S, Arvilommi H. Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain. Pediatr Res 1992;32:141–144.PubMedCrossRefGoogle Scholar
  31. Klein G, Pack A, Bonaparte C, Reuter G. Taxonomy and physiology of probiotic lactic acid bacteria. Int J Food Microbiol 1998;41:103–125.PubMedCrossRefGoogle Scholar
  32. Leistevuo T, Leistevuo J, Osterblad M, Arvola T, Toivonen P, Klaukka T, Lehtonen A, Huovinen P. Antimicrobial resistance of fecal aerobic gram-negative bacilli in different age groups in a community. Antimicrob Agents Chemother 1996;40:1931–1934.PubMedGoogle Scholar
  33. Lidbeck A, Gustafsson JA, Nord CE. Impact of Lactobacillus acidophilus supplements on the human oropharyngeal and intestinal microflora. Scand J Infect Dis 1987;19:531–537.PubMedCrossRefGoogle Scholar
  34. Link-Amster H, Rochat F, Saudan KY, Mignot O, Aeschlimann JM. Modulation of a specific humoral immune response and changes in intestinal flora mediated through fermented milk intake. FEMS Immunol Med Microbiol 1994;10:55–64.PubMedCrossRefGoogle Scholar
  35. Lundequist B, Nord CE, Winberg J. The composition of the faecal microflora in breast-fed and bottle fed infants from birth to eight weeks. Acta Paediatr Scand 1985;74:45–51.PubMedCrossRefGoogle Scholar
  36. McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL, Noorani Z et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994;271:1913–1918.PubMedCrossRefGoogle Scholar
  37. Mitra AK, Rabbani GH. A double-blind, controlled trial of Bioflorin (Streptococcus faecium SF68) in adults with acute diarrhea due to Vibrio cholerae and enterotoxigenic Escherichia coll. Gastroenterology 1990;99:1149–5112.PubMedGoogle Scholar
  38. Morrow AL, Pickering LK. Human milk protection against diarrheal disease. Semin Pediatr Infect Dis 1994;5:236–242.Google Scholar
  39. Morrow AL, Pickering LK. Human milk and infectious diseases. In: Long SS, Pickering LK, Prober CG, editors. Principles and Practice of Pediatric Infectious Diseases. London: Churchill-Livingstone; 1997. pp 87–95.Google Scholar
  40. Newburg DS. Oligosaccharides and glycoconjugates in human milk: their role in host defense. J Mammary Gland Biol Neoplasia. 1996;1:271–283.PubMedCrossRefGoogle Scholar
  41. Ogawa K, Ben RA, Pons S, de Paolo MIL,Fernandez LB. Volatile fatty acids, lantic acid and pH in the stools of breast-fed and bottle-fed infants. J Pediatr Gastroenterol Nutr 1992;15:248–262.PubMedCrossRefGoogle Scholar
  42. Oksanen PJ, Salminen S, Saxelin M, Hamalainen P, Ihantola-Vormisto A, Muurasniemi-Isoviita L, Nikkari S, Oksanen T, Porsti I, Salminen E et al. Prevention of travellers’ diarrhoea by Lactobacillus GG. Ann Med 1990;22:53–56.PubMedCrossRefGoogle Scholar
  43. Pabst HF, Spady DW. Effect of breast-feeding on antibody response to conjugate vacines. Lancet 1990;336:269–270.PubMedCrossRefGoogle Scholar
  44. Pearce JL, Hamilton JR. Controlled trial of orally administered lactobacilli in acute infantile diarrhea. J Pediatr 1974;84:261–262.PubMedCrossRefGoogle Scholar
  45. Pickering LK, Granoff DM, Erickson JR, Masor ML, Cordle CT, Schaller JP, Winship TR, Paule CL, Hilty MD. Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics 1998;101:242–249.PubMedCrossRefGoogle Scholar
  46. Raza S, Graham SM, Allen SJ, Sultana S, Cuevas L, Hart CA. Lactobacillus GG promotes recovery from acute non-bloody diarrhea in Pakistan. Pediatr Infect Dis J 1995;14:107–111.PubMedCrossRefGoogle Scholar
  47. Reid G, Bruce AW, McGroarty JA, Cheng KJ, Costerton W. Is there a role for lactobacilli in prevention of urogenital and intestinal infections? Clin Microbiol Rev 1990;3:335–344.PubMedGoogle Scholar
  48. Reuter G. Present and future of probiotics in Germany and in Central Europe. Biosci Microflora 1997;16:43–51.Google Scholar
  49. Rotimi VO, Duerden BI. The development of the bacterial flora in normal neonates. J Med Microbiol 1981; 14:51–62.PubMedCrossRefGoogle Scholar
  50. Saavdra J. Microbes to fight microbes: a not so novel approach to controlling diarrheal disease. J Pediatr Gastroenterol Nutr 1995;21:125–129.CrossRefGoogle Scholar
  51. Saavdra JM, Bauman NA, Oung I,Perman JA, Yolken RH. Feeding of Bifidobacterium bifidium and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding to rotavirus. Lancet 1994;344:1046–1049.CrossRefGoogle Scholar
  52. Saint-Marc T, Rossello-Prats L, Touraine JL. Efficacite de Saccharomyces boulardii dans le traitement des diarrhees du SIDA. Ann Med Interne (Paris) 1991;142:64–65.Google Scholar
  53. Spiegel J, Rose R, Karabell P, Frankos V, Schmitt D. Safety and benefits of fructooligosaccharides as food ingredients. Food Tech 1994; Jan:85–89.Google Scholar
  54. Wunderlich PF, Braun L, Fumagalli I, D’Apuzzo V, Heim F, Karly M, Lodi R, Politta G, Vonbank F, Zeltner L. Double-blind report on the efficacy of lactic acid-producing Enterococcus SF68 in the prevention of antibiotic-associated diarrhoea and in the treatment of acute diarrhoea. J Int Med Res 1989;17:333–338.PubMedGoogle Scholar
  55. Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics 1983;72:317–321.PubMedGoogle Scholar
  56. Yuhara T, Isojima S, Tsuchiya F, Mitsuoka T. On the intestinal flora of bottle-fed infant. Bifidobacteria Microflora 1983;2:33–39.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Larry K. Pickering
    • 1
  1. 1.National Immunization ProgramCenters for Disease Control and PreventionAtlanta

Personalised recommendations